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Time for a Human Interactome Project?
An investment of $100 million should be enough to correlate the genome with function, and identify new basic research and drug targets
MapQuest and global positioning systems have radically changed the way we travel. By showing us where we are relative to where we want to go, these tools simplify the job of getting from point A to point B, and make travel in unfamiliar places less stressful. Some years ago I realized molecular biologists face an analogous problem: Cells contain tens of thousands of proteins and other macromolecules, which mediate hundreds of thousands of physical interactions at any given moment. Yet biologists lacked the navigational aids to traverse those interaction networks, aids that travelers today take for granted.
For more than 50 years scientists like Max Delbrück and Conrad H. Waddington have been proposing models based on the idea that macromolecules form complex networks of functionally interacting components, and suggesting that the molecular mechanisms underlying most biological processes correspond to particular steady states adopted by such cellular networks.
Such systems-level conjectures complement molecular biology's reductionist, one-gene/one-function point-of-view in several ways. First, they provide a framework for understanding general biological properties like robustness and adaptability. It is unclear, for example, why more than half of all unique yeast genes (i.e., those without any recognizable genomic homolog) are dispensable for viability. These models also address limitations of the one-gene/one-function paradigm, such as the "gene number paradox": how species as different in complexity as worms and humans could contain approximately the same number of genes.
Systems-level models also provide testable hypotheses to explain, and not merely describe, cellular events like differentiation and homeostasis. Finally, they could aid early drug development, by considering a drug's actions in the context of the cellular networks in which the drug target functions.